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Heikki Helin

Publications and source records attributed to Heikki Helin.

13 recordsLinked to original sources
PubMed2005

Web-based virtual microscopy in teaching and standardizing Gleason grading.

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.

Biopsy, Needle↗
PubMed2005

Nordic immunohistochemical quality control.

The use of immunohistochemistry by pathologists has been steadily, almost logarithmically increasing during the last decade. There is no scientific indication that this trend will reverse or slow down. At the same time, quality control issues have not followed this tempo. In particular, external quality control has been neglected. In 1999, nine Scandinavian laboratories established organization, Nordic Quality Control (NordiQC), to provide external quality control in immunohistochemistry for Denmark, Norway, Sweden, and Finland. This commentary briefly describes the work of this organization.

Humans↗
PubMed2004

Uric acid correlates with the severity of histopathological parameters in IgA nephropathy.

BACKGROUND: Immunoglobulin-A nephropathy (IgAN) is the most common chronic glomerulonephritis worldwide. Many clinical and histopathological risk factors for progression have been found previously. Recently, metabolic risk factors, such as hyperuricaemia and hypertriglyceridaemia, also have been associated with the progression of IgAN. METHODS: In the present study we correlated clinical and metabolic risk factors with histopathological parameters in 202 patients with IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue were semiquantitatively graded into three classes. Mesangial proliferation activity and the amount of inflammatory cells were also evaluated by immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings. Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE), blood pressure and body mass index (BMI) were measured. Smoking habits and occurrence of diabetes mellitus also were evaluated. The independent role of serum uric acid in the development of renal morphological changes was evaluated in multivariate analysis. RESULTS: Serum uric acid and UPE level correlated with several histological parameters. Uric acid level showed the strongest correlation with tubulointerstitial changes and UPE with glomerulosclerosis. The level of serum triglycerides correlated with interstitial fibrosis and hyaline arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis, glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus correlated with both tubulointerstitial and vascular changes. We found no significant correlations between histopathological parameters and smoking habits or serum cholesterol level. Serum uric acid had independent associations with the presence of tubular atrophy and interstitial fibrosis and inflammation. CONCLUSIONS: We conclude that many metabolic factors are univariately associated with renal morphological findings in IgAN. These same factors are central in the metabolic or insulin resistance syndrome and may have a pathogenetic role in the progression of IgAN. Serum uric acid may have an independent role in development of tubulointerstitial lesions as well as being associated with inflammation in renal tissue of patients with IgAN.

Adolescent↗
PubMed2004

Renal cell carcinoma MIB-1, Bax and Bcl-2 expression and prognosis.

PURPOSE: Proliferation and programmed cell death (apoptosis) are key factors in oncogenesis and tumor progression. In carcinogenesis important regulators of apoptosis are members of the Bcl-2 family. In this family the Bcl-2 gene has an inhibitory effect on apoptosis, while Bax promotes cell death. In renal cell carcinoma (RCC) the associations between Bcl-2 proteins and RCC prognosis have been controversial. We evaluated Bax and Bcl-2 levels in RCC, and their associations with prognosis, proliferation and traditional prognostic factors. MATERIALS AND METHODS: Our prospective study population comprised 138 consecutive patients who underwent radical nephrectomy for RCC. Immunostaining and semiquantitative indices for Ki-67 (MIB-1), Bax and Bcl-2 were estimated. Their associations with prognosis were explored. RESULTS: On univariate analysis according to survival statistically significant differences were achieved by Bax (positive vs negative HR 3.04, 95% CI 1.27 to 7.23), Bcl-2 (positive vs negative HR 0.43, 95% CI 0.23 to 0.81), MIB-1 (continuous HR 1.03, 95% CI 1.001 to 1.064), Fuhrman nuclear class (4 vs 1 plus 2 HR 8.15, 95% CI 3.13 to 21.20) and stage (4 vs 1 HR 60.04, 95% CI 13.99 to 257.68). Only stage (HR 47.96, 95% CI 10.85 to 212.03) and Fuhrman classification (HR 4.32, 95% CI 1.60 to 11.65) attained statistical significance on Cox regression multivariate analysis. CONCLUSIONS: In our prospective study Bax and Bcl-2 showed a statistically significant association with prognosis in RCC but did not achieve the status of independent prognostic factors. Further studies are needed to clarify the role of the apoptotic process in tumor progression and prognosis.

Adult↗
PubMed2004

High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure.

BACKGROUND: Calcium salts are used as phosphate binders in renal failure, while high calcium diet also improves vasorelaxation and enhances natriuresis. The influences of calcium intake on renal renin-angiotensin system (RAS) are largely unknown. METHODS: Four weeks after NTX, rats were put on 3.0% or 0.3% calcium diet for 8 weeks (12-week study). In additional experiments, 15 weeks after NTX, rats were put on similar diets for 12 weeks (27-week study). Appropriate blood, urine, and kidney samples were taken. Renal angiotensin-converting enzyme (ACE) and angiotensin II receptors (AT1, AT2) were examined using autoradiography, ACE also using Western blotting, and connective tissue growth factor (CTGF) using immunohistochemistry. RESULTS: In the 12-week study, albuminuria increased 5-fold in NTX rats, but only 2-fold in calcium NTX rats on 3.0% calcium. In the 27-week study, high calcium intake decreased blood pressure, retarded progression of renal failure, reduced glomerulosclerosis, interstitial damage, and aortic calcifications, and improved survival from 50% to 92% in NTX rats. In both experiments plasma parathyroid hormone and phosphate were elevated after NTX, and suppressed by high calcium diet, while kidney ACE was down-regulated by 40% or more after increased calcium intake. In the 27-week study renal CTGF was decreased and cortical AT1 receptor density reduced after high calcium diet. CONCLUSION: High calcium diet down-regulated kidney ACE, reduced albuminuria and blood pressure, and favorably influenced kidney morphology in experimental renal failure. These findings suggest a link between calcium metabolism and kidney ACE expression, which may play a role in the progression of renal damage.

Albuminuria↗
PubMed2003

Arm-specific multicolor fluorescence in situ hybridization reveals widespread chromosomal instability in glioma cell lines.

An investigation of numerical and structural chromosome aberrations using chromosome arm-specific multicolor fluorescence in situ hybridization (armFISH) revealed considerable genetic heterogeneity among and within 11 glioma cell lines. Despite the substantial variation in numerical chromosome alterations among the cell lines, several distinct and glioma growth-associated losses or gains were frequently observed, that is, losses of chromosomes 10, 13, and 22 and gain of chromosome 7 in particular. Structural aberrations frequently affected chromosomes 1, 4, 7, 16, and 19; however, no single structural chromosome aberration common to all or even several glioma cell lines could be found. Structural alterations were often multiform, and a large variety of unstable chromosome structures were detected. Two of the cell lines also harbored small marker chromosomes containing mainly heterochromatin and chromosomal insertions within hetero-chromatic regions. Altogether, the armFISH provides a versatile tool for the identification of chromosomal aberrations as well as their formation patterns in tumors with a complex genome at the level of chromosome arms.

Brain Neoplasms↗
PubMed2003

Comparison of computed tomography and systematic lymph node dissection in determining TNM and stage in non-small cell lung cancer.

OBJECTIVE: To compare computed tomography (CT)-based clinical TNM and staging to surgical-pathological staging with systematic lymph node dissection in primary non-small cell lung cancer. METHODS: The study included 49 non-small cell lung cancer patients that underwent lung resection and systematic lymph node dissection between 1997 and 2001. Preoperative clinical and CT findings were compared with surgical-pathological findings. Lymph nodes with a shortest diameter of over 1 cm on CT were considered abnormal, but did not contraindicate surgery. Patients with CT indicating an invasive T4 tumor, pleural carcinosis, or bulky N2 disease were excluded. RESULTS: Sixty-five percent (32/49) had epidermoid carcinoma, and 25% (12/49) had adenocarcinoma. N2 metastases were found in 12% (6/49). The clinical T category was correct in 71% (35/49), and the N category in 55% (27/49). The sensitivity for detecting N2 disease was 67% (4/6), and the specificity was 81% (35/43). The positive predictive value for N2 disease was 33% (4/12), and the negative predictive value was 95% (35/37). Node-by-node agreement on N2 metastatic location was 17% (1/6). Skip N2 metastases without any N1 involvement were found in 4% (2/49), or 33% (2/6) of all N2 cases. The clinical stage was correct in 45% (22/49), and complete TNM agreement was 37% (18/49). CONCLUSIONS: The clinical TNM and staging based on CT are inaccurate. The sensitivity for detecting N2 disease is poor, especially on node-by node basis. Preoperative exclusion of N2 metastases is quite reliable, but a positive finding should always be verified. Systematic mediastinal lymph node dissection is necessary to detect N2 metastases inaccessible to cervical mediastinoscopy, and skip N2 metastases without N1 involvement.

Aged↗
PubMed2003

IgM nephropathy: clinical picture and long-term prognosis.

BACKGROUND: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis with mesangial hypercellularity and diffuse IgM deposits. METHODS: We studied clinical presentation, morphological findings, and prognostic factors in 110 patients with IgM nephropathy without systemic diseases. The series included both pediatric and adult patients with nephrotic syndrome (NS) or minor urinary abnormalities. RESULTS: Mean postbiopsy follow-up was 8 years. During 15 years of follow-up, 36% of patients developed renal insufficiency and 23% reached end-stage renal failure. In multivariate analysis, hypertension at the time of renal biopsy was the only significant risk factor for renal insufficiency. Of histological parameters, interstitial fibrosis had the strongest prognostic value. Hypertension was diagnosed in 50% of patients with a postbiopsy follow-up of 15 years. Twenty-nine percent of nephrotic patients had disease resistant to corticosteroids, whereas 80% of patients with steroid-sensitive disease were steroid dependent. Eleven patients, 8 patients with NS and 3 patients with asymptomatic proteinuria, underwent repeated renal biopsy. In five samples, typical morphological characteristics of focal and segmental glomerulosclerosis were seen. CONCLUSION: We propose that IgM nephropathy can be divided into two subgroups with similar renal biopsy findings, but differences in sex distribution and initial presentation.

Adolescent↗
PubMed2003

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure.

Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium (n = 10-11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake.

Animals↗
PubMed2003

The immunohistochemical characterisation of an SV40-immortalised human corneal epithelial cell line.

Alternatives to the Draize rabbit eye irritation test are currently being investigated. Because of morphological and biochemical differences between the rabbit and the human eye, continuous human cell lines have been proposed for use in ocular toxicology studies. Single cell-type monolayer cultures in culture medium have been used extensively in ocular toxicology. In the present study, an SV40-immortalised human corneal epithelial (HCE) cell line was characterised immunohistochemically, by using 13 different monoclonal antibodies to cytokeratins (CKs), ranging from CK3 to CK20. The results from the monolayer HCE cell cultures were compared with those from the corneal epithelium of human corneal cryostat sections. Previous studies have shown that the morphology of the HCE cell is similar to that of primary cultured human corneal epithelial cells, and that the cells express the cornea-specific CK3. In the study reported here, we show that the cell line also expresses CKs 7, 8, 18 and 19. These CKs are typically expressed by simple epithelial cells, and are not found in the human cornea in vivo. Therefore, the monolayer HCE cell line grown in culture medium does not express the CK pattern that is typical of human corneal epithelium. This should be taken into consideration when using HCE cell cultures in similar single cell-type experiments for ocular toxicology.

Animal Use Alternatives↗
PubMed2002

Cancer incidence in families with multiple glioma patients.

Twenty-four Finnish families with 2 or more glioma patients were identified through questionnaires sent to 369 consecutive glioma patients receiving surgery at Tampere University Hospital during 1983-94. To explore whether unusual cancer susceptibility is involved, the cancer risk of 2,664 family members was estimated using population-based data from the Finnish Cancer Registry. Among the total cohort of relatives, 88 cancers were observed during 1953-97. The overall cancer risk among 12 families with juvenile onset gliomas was significantly decreased (standardized incidence ratio [SIR] 0.6, 95% confidence interval [CI]: 0.4-0.9). Among 12 families with adult onset gliomas, the overall cancer risk was equal to that of the reference population (SIR 1.1, 95% CI: 0.8-1.4) whereas the risk of skin melanoma (SIR 4.0, 95% CI: 1.5-8.8) and meningioma (SIR 5.5, 95% CI: 1.1-16) were significantly increased. Several other tumors, including those associated with neurofibromatosis 1 and 2, tuberous sclerosis and Li-Fraumeni and Turcot syndromes were surveyed, but no elevated risks were observed. In conclusion, the presence of meningiomas and skin melanomas in glioma families may indicate a novel association as a cancer susceptibility trait.

Adult↗
PubMed2002

The establishment of a network of European human research tissue banks.

This is a report of a workshop held on the establishment of human research tissue banking which was held in Levi, Finland 21-24 March 2002. There were 21 participants from 7 European countries. This meeting was attended by representatives from academia, research tissue banks and from the Biotech and Pharmaceutical Industries. The principal aim of the workshop was to find a way to progress the recommendations from ECVAM workshop 44 (ATLA 29, 125-134, 2001) and ECVAM workshop 32 (ATLA 26, 763-777, 1998). The workshop represented the first unofficial meeting of the European Network of Research Tissue Banks (ENRTB) steering group. It is expected that in the period preceding the next workshop the ENRTB steering group will co-ordinate the ethical, legislative and organisational aspects of research tissue banking. Key issues dealt with by the Levi workshop included the practical aspects of sharing expertise and experiences across the different European members. Such collaboration between research tissue banks and end users of such material seeks to ultimately enable shared access to human tissue for medical and pharmaco-toxicological research while maintaining strict adherence to differences in legal and ethical aspects related to the use of human tissue in individual countries.

Journal Article↗